Neratinib is an anti-breast cancer drug developed by Wyeth (Pfizer), and then produced by Puma Biotechnology who gets the development rights from Pfizer. It is an oral, irreversible pan-ErbB receptor tyrosine kinase inhibitor, and it can effectively inhibit the activity of ErbB1 and ErbB2 tyrosine kinase. The chemical name of Neratinib is: (2E)-N-[4-[[3-chloro-4-[(pyridin-2-yl)methoxy]phenyl]amino]-3-cyano-7-ethoxyquinolin-6-yl]-4-(d imethylamino)but-2-enamide, and the structure is shown as Formula (I):

At present, CN101918390B disclosed several salts of Formula (I), including maleate, fumarate, mesylate, p-tosylate, succinate, sulfate, tartrate, and citrate. Physical and chemical properties of these salts were evaluated in the patent, wherein maleate salt exhibited the best physical and chemical properties. However, CN101918390B disclosed only three crystalline forms of maleate, among which Form III is a partly hydrate (a mixture of Form I and Form II); Form I is an anhydrate but can easily convert to Form II by absorbing moisture in the air. So Form I is not suitable for long-term storage. Only Form II can be used for commercial production. Therefore, it is necessary to develop novel crystalline forms which have good stability and higher solubility than maleate Form II in CN101918390B.
The present invention develops novel crystalline forms of maleate which have good stability, high solubility, low hygroscopicity, and are suitable for storage and commercial production. The present invention provides more and better choice for the follow-up development of the drug, and meets the development needs of the drug.